Researcher: Dr Sebastian Zeki, Barts and the London School of Medicine

Project Title: Clonal Competition and Genetic Evolution of Barrett's Oesophagus

Three Year Training Fellowship - commenced August 2010

Barrett's oesophagus (BO) is a common condition in which the cells lining the oesophagus change type in response to acid and bile reflux. This change is an important risk factor for oesophageal cancer development. The cells in BO can develop mutations in their DNA which can lead to cancer. Different cells develop different mutations and these cells may compete against one other to develop into a cancer. This project aims to investigate whether this competition occurs and what mechanisms it involves by studying mutations in small areas of tissue and determining how colonies of cells with the same mutation compete against other cells in tissue from patients with BO.

The implications of this research are
1. Determining factors that can predict who will respond to therapies such as radiofrequency ablation by determining the kind of mutation they have before treatment has started
2. Determining that competitive processes exist in the oesophagus may allow exploration of a new area within gastrointestinal biology. Efforts may therefore be concentrated on how to alter competitive signalling between cells so that the stronger populations (more likely to develop into cancer) no longer have the competitive advantage.

Researcher: Dr Newton Wong, John Radcliffe Hospital, Oxford

Project Title: A Study of the Molecular Pathogenesis and Progenitor Cell of Barrett's Metaplasia

Two Year Training Fellowship - completed February 2004

Barrett's metaplasia (BM) is an abnormal change in the lining of the lower end of the oesophagus. BM is quite common and can be found in up to 1 in every 100 adults. The frequency of MB still appears to be rising. The main problem with BM is that it can give rise to cancer of the gullet. Indeed, it has been shown that 1 of every 20 adults with BM will eventually develop such cancer. As a result, the increasing frequency of BM has also seen a rise in the frequency of cancer of the oesophagus.

BM appears to be caused by reflux (backflow) of stomach and intestinal contents into the throat. However, it is uncertain which components of these refluxing contents are important in causing BM. Little is also known about the molecules and mechanisms that are involved in the formation of BM.

This research studied tissue samples from patients with BM. The samples were examined to determine which molecules are expressed in BM. The samples were then used to try to reproduce the development of BM in the laboratory. This allowed for detailed study of which refluxing contents, molecules and mechanisms are important to BM in the hope that the findings might lead to the development of ways to identify those patients at greatest risk of developing BM and new treatments to stop the BM causing cancer.